Abstract

Aims/hypothesis. Thiazolidinediones are reported to improve pancreatic islet morphology and beta-cell function in rodents, supporting the hypothesis of a direct action of thiazolidinediones on endocrine islet cells. In this study we examined the expression of the peroxisome proliferator-activated receptor γ, a nuclear receptor that is activated by naturally occurring fatty acids and synthetic thiazolidinediones, in normal human endocrine pancreatic cells. Methods. Human islets were isolated from pancreata harvested in ten brain-dead lean non-diabetic adult donors. We analysed the gene and protein expression of the human peroxisome proliferator-activated receptor γ and evaluated the effects of peroxisome proliferator-activated receptor γ agonist on insulin secretion in human islet preparations. Results. The RT-PCR carried out on total RNA from four distinct human islet preparations demonstrated the presence of peroxisome proliferator-activated receptor γ mRNA. Western blot analysis showed the consistent expression of peroxisome proliferator-activated receptor γ protein. Peroxisome proliferator-activated receptor γ was shown to be present in all three endocrine cell types studied (alpha, beta and delta cells) by immunohistochemistry. Conclusion/interpretation. We found that peroxisome proliferator-activated receptor γ is highly expressed in human islet endocrine cells, both at the mRNA and protein levels. These results support the hypothesis of a direct influence of peroxisome proliferator-activated receptor γ agonist on human pancreatic endocrine cells. [Diabetologia (2000) 43: 1165–1169]